2022 UGRA Spring Forum Speaker Presentation Summary

Posted on Sunday, May 29th, 2022

2022 UGRA Spring Forum Speaker Presentation Summary

By Pat Shewen

The Spring Forum speakers addressed current information about COVID-19. First, current UGRA President, University Professor Emeritus Peter Krell, a virologist, reflected on what we know about the virus itself, vaccines, antivirals, challenges and counter measures, after two plus years. Then, Professor Maya Goldenberg of the Department of Philosophy, discussed her research on vaccine hesitancy, which for many years focused on hesitancy to pediatric vaccines and more recently examined resistance to COVID vaccination.

Dr. Krell provided an early timeline for SARS-CoV-2, which causes COVID-19. Initially revealed in Wuhan in December 2019, retrospective studies showed earlier emergence in Brazil. By January 2020, The Wuhan Institute of Virology had grown the virus in cell culture and identified the receptor as ACE2. The complete RNA sequence of the virus was released to a public database, GISAID by Professor Yong-Zhen Zhang of Shanghai. Shortly after, Robert Kozak at Sunnybrook, following technical advice from Drs. Krell and Nagy at Guelph, first grew, and then sequenced the first Canadian isolate. Rapid virus isolation, sequencing and the ability to grow in culture, led to rapid development of molecular diagnostics (e.g., PCR) vaccines and antiviral therapies.

Of the first 174 cases, most traced back to live animal markets in Wuhan, with evidence of person-to- person transmission. International studies published in Nature in 2022 confirmed an environmental origin, implicating raccoon dogs as a possible source, and dispelling rumors of the inadvertent release of a laboratory strain.

Canadian data over the past two years revealed that 8.6% of cases occurred in people over 70, although they represent 12.6% of the population. Fewer cases than expected by chance. However, people over 70 represent 46% of hospitalizations, 33% of ICU cases and 82% of deaths. Thus, the impact of infection is far more serious in this demographic.

SARS-CoV-2 is a large RNA virus encased in a protein shell. Its genome comprises 29,903 nucleotides (10 genes). These are the instruction manual for replication of its RNA and proteins, and virus assembly, once it infects a host cell. In copying the manual, errors can occur leading to changes (mutations) in the virus produced. The major outer shell of the virus carries and displays Spike protein, Envelope protein and Matrix protein. Spike protein is responsible for attachment to the ACE2 receptor on host cells, expressed primarily on vascular endothelia, renal and cardiovascular tissue, and the epithelia of the lung and small intestine. The Spike protein is, therefore, a major target of the immune system. Antibodies attached to Spike protein block virus attachment to ACE2 preventing infection of the cell. The spikes protrude on the surface of the virus particle (virion) and look like a crown, or corona, when viewed by an electron microscope. Hence, CORONA is the name for this family of viruses.

Some mutations of RNA coding for the Spike protein result in production of a new variant of the virus, that may more easily bind to ACE2, increasing infectivity and contagion, or may fail to be recognized by some (but not typically all) antibodies produced in response to infection or vaccination with the original version. New variants lead to new waves of infection and hospitalization. Canada experienced the first COVID wave from April to July 2020, by the variant named alpha (α). Alpha/beta (α/β) produced a second wave early in 2021, Beta/gamma (β/γ) caused a third wave in late spring and early summer> of 2021. Delta (δ) induced a smaller peak in fall 2021. Then omicron (ο), a highly contagious variant, caused a major spike in hospitalizations in early 2022. Currently, we are experiencing another spike of οBA.2, a variant of omicron. The longer the virus continues to infect, reproduce and transmit, the more opportunity there is for mutation and the greater the chance of accumulating dangerous variants (variants of concern).

Vaccination has proven to be one of the most successful medical interventions, responsible for much of the rise in life expectancy in Canada from 71 in 1960 to 82 in 2021. The 25 vaccine-preventable diseases in Canada range from smallpox (eradicated in 1978), to polio and several other primarily childhood diseases, to cancers (papillomavirus). These ‘conventional’ vaccines utilize the actual virus or bacterium, modified or killed, a closely related cousin that is not pathogenic in humans, or some component of the organism. The use of cowpox virus to induce immunity against smallpox, gave us the term ‘vaccine’ (vacca=cow in Latin).

In the quest to produce vaccines that are safer and less expensive to manufacture, more modern technologies are being examined. Development of mRNA (messenger RNA) vaccines was already quite advanced when COVID hit. In all living cells, mRNA delivers the code from each gene for synthesis of the proteins used for cell, and also virus, replication. For vaccination purposes, the vaccine delivers the code for production of virus Spike protein into the arm. It is taken up by host cells that then produce the virus’ Spike protein. This protein is recognized as foreign and antibodies are produced in response. The antibodies bind Spike protein and block its attachment to ACE2, thereby limiting infection if the host is exposed to the actual virus. Quick response in the vaccinated host means less transmission of virus, reduction in serious disease and death. Moderna and Pfizer use the same mRNA platform and were able to quickly pivot to produce a COVID vaccine since much of the preliminary work was already complete.

Other companies created virus-vectored vaccines, in which the gene for the virus of interest, Spike protein, is inserted into a non-pathogenic virus. After injection, this recombinant virus expresses Spike protein, stimulating an immune response. Janssen (Johnson and Johnson) uses a non-replicating human adenovirus (Ad26) as the vector. Oxford/AstraZeneca uses a chimpanzee adenovirus, while Sputnik combines Ad26 and the chimpanzee adenovirus. Nuvaxovid uses insect baculoviruses to produce spike protein nanoparticle rosettes and combines it with an adjuvant to enhance the immune response. This is the vaccine to be produced at the Biologic Manufacturing Centre in Montreal in 2022. Several other Canadian companies and universities continue to work on novel vaccine development.

Canadian data indicate that COVID-19 vaccines work, reducing disease, hospitalizations, and death. Over the two years of the pandemic, about 60% of hospitalizations and death occurred in unvaccinated individuals. (https://health-infobase.canada.ca/covid-19/epidemiological-summary-covid-19- cases.html).

Antiviral drugs, like Remdesivir and Molinopiravir, target the virus RNA causing deleterious mutations or errors in the RNA copies and production of defective virus proteins. They must be given soon after infection and are expensive. Paxlovid (Pfizer) interferes with viral RNA replication and must be given within five days of exposure. Evusheld (AstraZeneca) is comprised of two artificial monoclonal antibodies that bind different regions of the Spike protein. It is used prophylactically to prevent infection in immunocompromised patients.

What have we learned? Like many respiratory diseases, COVID-19 is spread mainly by aerosol droplets. Masks, improved ventilation and air filtration (HEPA filters) reduce aerosol transmission. Dr. Krell suggested that restrictions/mandates are most effective when imposed early, when a rise is first detected, and that restrictions should not be relaxed until cases plateau and then should be lifted only gradually. Education in civics, public health, and critical thinking are needed for people to understand why and when restrictions should be imposed. In addition, funding for Canadian vaccine development and manufacturing will help ensure vaccine availability in the future.

Dr. Goldenberg’s fundamental philosophical question is “How do we know what to believe?” In the context of health care, this impacts the transfer of health care information to the patient, and can have profound impact on patient well-being and public health. She sees vaccine hesitancy as indicative of poor public trust in scientific institutions. Trust is key to successful public health intervention, but scientists must EARN public trust rather than expect it. It is this lack of trust rather than lack of scientific information that leads to vaccine hesitancy, and this applies to all science not just vaccines. Previous thinking adhered to the knowledge deficit model that assumes scientific illiteracy or science denial as an underlying cause of mistrust. Misunderstandings and misconceptions can be overcome with more public education. This model has not worked. One key finding in examining its failure is our lack of understanding that science is an evolving process, not a series of hard facts (Neil deGrasse Tyson).

Pediatric vaccine hesitancy does not come from a lack of sophistication. In developed countries, most reluctant parents are well-educated white mothers. They are well-read, critical thinkers, who, reading between the lines, suspect that public health decisions are unduly influenced by the profit-driven motives of “big pharma”, rather than genuine medical concerns. While racialized people are justifiably less willing to believe medical authorities, based on historical exploitation, most of those surveyed did vaccinate their children. However, historical mistrust did influence hesitancy to COVID vaccination in this group.

There are two approaches used to counter vaccine refusal. The first is ‘persuasion’ by improving general knowledge about the disease and vaccines and stirring a sense of community responsibility for herd immunity. This approach has little impact in changing attitudes, partly because public health agencies are underfunded to do this this effectively. The second is ‘regulation’ that has been justified for pediatric vaccination as necessary to protect all vulnerable children, not just those who have been vaccinated. Pediatric vaccination for daycare and school entry has been the law in Ontario since 1982, with limited exemptions for religious or personal beliefs. Consequences for failure to vaccinate include suspension from school or being barred from other services. Physicians may remove unvaccinated children and their families from their practice. In Australia, failure to vaccinate results in loss of government child benefits. Public shaming of anti-vaxxers adds further negative pressure. In the case of COVID vaccination, restrictions on access to university and college campuses, restaurants, and travel, as well as mandated vaccination for public sector workers and those caring for vulnerable populations resulted in increased uptake of vaccines. In some countries and American states, non-medical exemptions for pediatric or COVID vaccines are not allowed. Ontario has taken a softer approach, though for COVID vaccines the criteria for exemption are quite strict. For pediatric vaccines, one must submit a notarized statement of ‘conscientious and religious beliefs’. Since 2016, consultation with a physician is required and, since 2018, attendance at a public health education session is needed before permission is granted.

Ethically, public health authorities try to take a balanced approach weighing individual liberties against protecting the health of the community. Imposing strict mandates only when necessary (e.g., for measles outbreaks), they opt for the least restrictive action to achieve the desired goals rather than coercive measures.

For more in depth reading, see A Shot to Save the World by Gregory Zuckerman (Penguin Random House, 2021) and Dr. Goldberg’s recent book Vaccine Hesitancy, Public Trust, Expertise and the War on Science (University of Pittsburgh Press, 2021).

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